Synergistic metabolic modulation of fibroblast-like synoviocytes via targeted dual prodrug nanoparticles to mitigate rheumatoid arthritis DOI Creative Commons
Shaobing Li, Jun‐Tao Lin, Chengxinqiao Wang

и другие.

Acta Pharmaceutica Sinica B, Год журнала: 2024, Номер 15(1), С. 542 - 556

Опубликована: Ноя. 18, 2024

Elevated glucose metabolism is a prominent characteristic of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA). However, the efficacy inhibiting single target FLS using small molecular inhibitors limited for RA treatment. Herein, synergistic inhibition FLS' survival, proliferation, and activation by combining two inhibitors, diclofenac (DC) lonidamine (LND) was first verified. Subsequently, DC LND were individually conjugated to cystamine-modified hyaluronic acid (HA) prepare polymer-prodrug conjugates. A HAP-1 peptide-modified dual conjugates-assembled nanoparticles system (HAP-1NPDC+LND) further tailored optimal ratio targeted metabolic modulation alleviate symptoms. Upon uptake inflamed joints, HAP-1NPDC+LND released within intracellular reductive microenvironment, where hinders suppresses glycolytic enzymes eliminate synergistically. Additionally, secretion lactic pro-inflammatory factors from reduced, thereby disrupting crosstalk between macrophages. Finally, demonstrated promising mouse model collagen-induced (CIA). Overall, this research provides valuable insights into novel therapeutic strategies safe effective treatment through FLS.

Язык: Английский

Role of Chinese Medicine Monomers in Dry Eye Disease: Breaking the Vicious Cycle of Inflammation DOI Creative Commons

Zhuoyu Hu,

Xiangdong Chen, Qi Hu

и другие.

Pharmacology Research & Perspectives, Год журнала: 2025, Номер 13(2)

Опубликована: Фев. 20, 2025

Dry eye disease (DED) is a chronically inflammatory ocular surface disorder of unknown pathogenesis. Anti-inflammatory medications, artificial tears, autologous serum, and LipiFlow have been shown to be highly beneficial in alleviating symptoms. Nevertheless, these interventions often provide only short-term results do not address the underlying problems disease. There growing evidence that risk DED associated with vicious cycle inflammation. This inflammation produced by interaction several factors, including tear film hyperosmolarity, instability, inflammation, apoptosis. Chinese medicine monomers, distinguished their multicomponent multitarget advantages, help treat modulating status, inhibiting responses, apoptosis, providing new way thinking management medicine.

Язык: Английский

Процитировано

0

Network Pharmacology-Based Strategy Integrated with Molecular Docking and In Vitro Experimental Validation to Explore the Underlying Mechanism of Fangji Huangqi Decoction in Treating Rheumatoid Arthritis DOI Creative Commons
Weijin Zhang, Hui Guo, Leyuan Li

и другие.

ACS Omega, Год журнала: 2024, Номер 9(29), С. 31878 - 31889

Опубликована: Июль 10, 2024

decoction (FHD), as a classic traditional Chinese medicine formula, has been clinically proven effective against rheumatoid arthritis (RA), yet its therapeutic mechanism remains unclear. This study employed network pharmacology and molecular docking methods to explore the major active components, biological targets, signaling pathways of FHD. Subsequently, lipopolysaccharide (LPS)-stimulated RAW264.7 cells were used in vitro model validate modulating effects FHD on molecules/inflammatory mediators using various biomedical techniques/kits such MTT assay, Griess reagents, flow cytometry, RT-qPCR, immunoblotting. Network analyses indicated total 20 components 30 core targets RA. Pathway enrichment demonstrated involvement mitogen-activated protein kinase (MAPK) efficacy formula. Furthermore, experimental evidence that dose-dependently significantly inhibited productions nitric oxide (NO) reactive oxygen species; lowered mRNA expression levels proinflammatory including iNOS, COX-2, TNF-α, ΙL-1β, IL-6; decreased phosphorylated forms p38, ERK, JNK, NF-κB p65. Additionally, results showed tetrandrine, licochalcone A, oxonantenine, isorhamnetin, kaempferol exerted potent capability binding target molecules focused pathway, probably being potential substances for Our integrated with cellular validation elucidated exerts downregulating MAPK ultimately leading inhibitory LPS-stimulated cells. work comprehensively substances, key involved anti-RA these findings provide further understanding underlying managing

Язык: Английский

Процитировано

3

Pro-differentiative, Pro-adhesive and Pro-migratory Activities of Isorhamnetin in MC3T3-E1 Osteoblasts via Activation of ERK-dependent BMP2-Smad Signaling DOI
Jing Li, Lili Sun,

Fanli Wang

и другие.

Cell Biochemistry and Biophysics, Год журнала: 2024, Номер 82(4), С. 3607 - 3617

Опубликована: Авг. 13, 2024

Язык: Английский

Процитировано

1

Chromosome‐level genome assembly of Iodes seguinii and its metabonomic implications for rheumatoid arthritis treatment DOI Creative Commons
Xun Gong, Hantao Zhang, Yong Guo

и другие.

The Plant Genome, Год журнала: 2024, Номер 18(1)

Опубликована: Ноя. 27, 2024

Abstract Iodes seguinii is a woody vine known for its potential therapeutic applications in treating rheumatoid arthritis (RA) due to rich bioactive components. Here, we achieved the first chromosome‐level assembly of nuclear genome I. using PacBio HiFi and chromatin conformation capture (Hi‐C) sequencing data. The initial with data produced contigs an N50 length 9.71 Mb, Hi‐C anchored these into 13 chromosomes, achieving total 273.58 closely matching estimated size. Quality assessments, including BUSCO, long terminal repeat index, transcriptome mapping rates, coverage, confirmed high quality, completeness, continuity assembly, identifying 115.28 Mb repetitive sequences, 1062 RNA genes, 25,270 protein‐coding genes. Additionally, assembled annotated 150,599 bp chloroplast Illumina data, containing 121 genes key DNA barcodes, maturase K ( matK ) proving effective species identification. Phylogenetic analysis positioned at base Lamiales clade, significant gene family expansions contractions, particularly related secondary metabolite synthesis damage repair. Metabolite identified 84 active components , discovery luteolin, 119 targets predicted RA treatment, core like AKT1 toll‐like receptor 4 TLR4 ), epidermal growth factor EGFR tumor necrosis TNF TP53 NFKB1 janus kinase 2 JAK2 BCL2 mitogen‐activated protein 1 MAPK1 spleen‐associated tyrosine SYK ). Key such as flavonoids polyphenols anti‐inflammatory activities were highlighted. particular, underscores role. These findings provide valuable genomic resource scientific basis development application addressing gap genus order Icacinales underscoring need further research genomics, transcriptomics, metabolomics fully explore potential.

Язык: Английский

Процитировано

1

From Tea to Functional Foods: Exploring Caryopteris mongolica Bunge for Anti-Rheumatoid Arthritis and Unraveling Its Potential Mechanisms DOI Open Access
Xin Dong, Zhi Wang, Yao Fu

и другие.

Nutrients, Год журнала: 2024, Номер 16(24), С. 4311 - 4311

Опубликована: Дек. 13, 2024

Background: Caryopteris mongolica Bunge (CM) shows promising potential for managing rheumatoid arthritis (RA) and digestive disorders, attributed to its rich content of bioactive compounds such as polyphenols flavonoids. Despite common use in herbal tea, the specific mechanisms underlying CM’s anti-inflammatory joint-protective effects remain unclear, limiting development a functional food. This study investigated aqueous CM extract on RA collagen-induced (CIA) rats explored mechanisms. Methods: Forty-eight female Sprague-Dawley were randomly assigned six groups (n = 8): normal control, CIA model, methotrexate (MTX), high-, middle-, low-dose groups. Anti-inflammatory evaluated using biochemical histological analyses. To elucidate mechanisms, we applied metabolomics, network pharmacology, transcriptomics approaches. Results: The results demonstrated that effectively suppressed synovial inflammation rats, reducing joint degradation. mediated through TNF signaling pathway, modulating glycerophospholipid amino acid metabolism, including reduced levels tryptophan, LysoPC, asparagine. Molecular docking identified scutellarin apigenin key compounds. Additionally, immunofluorescence analysis revealed therapeutic via inhibition suppression M1 macrophage polarization. Conclusions: These findings highlight support food or pharmaceutical product.

Язык: Английский

Процитировано

0

Synergistic metabolic modulation of fibroblast-like synoviocytes via targeted dual prodrug nanoparticles to mitigate rheumatoid arthritis DOI Creative Commons
Shaobing Li, Jun‐Tao Lin, Chengxinqiao Wang

и другие.

Acta Pharmaceutica Sinica B, Год журнала: 2024, Номер 15(1), С. 542 - 556

Опубликована: Ноя. 18, 2024

Elevated glucose metabolism is a prominent characteristic of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA). However, the efficacy inhibiting single target FLS using small molecular inhibitors limited for RA treatment. Herein, synergistic inhibition FLS' survival, proliferation, and activation by combining two inhibitors, diclofenac (DC) lonidamine (LND) was first verified. Subsequently, DC LND were individually conjugated to cystamine-modified hyaluronic acid (HA) prepare polymer-prodrug conjugates. A HAP-1 peptide-modified dual conjugates-assembled nanoparticles system (HAP-1NPDC+LND) further tailored optimal ratio targeted metabolic modulation alleviate symptoms. Upon uptake inflamed joints, HAP-1NPDC+LND released within intracellular reductive microenvironment, where hinders suppresses glycolytic enzymes eliminate synergistically. Additionally, secretion lactic pro-inflammatory factors from reduced, thereby disrupting crosstalk between macrophages. Finally, demonstrated promising mouse model collagen-induced (CIA). Overall, this research provides valuable insights into novel therapeutic strategies safe effective treatment through FLS.

Язык: Английский

Процитировано

0